Azoles and azines: CXIX. Alkylation of 5,5′-(4-nitrobenzylidene) bis(2-thiobarbituric) acid and 5-(4-nitrophenyl)-2,8-dithioxo-5,7,8,9- tetrahydro-2H-pyrano[2,3-d:6,5-d′]dipyrimidine-4,6(1H,3H)-dione with haloacetic acids and their esters

Article abstract of DOI:10.1023/B:RUGC.0000025180.58032.54

5,5′-(4-Nitrobenzylidene)bis(2-thiobarbituric) acid and 5-(4-nitrophenyl)-2,8-dithioxo-5,7,8,9-tetrahydro-2H-pyrano[2,3-d:6,5-d′] dipyrimidine-4,6(1H,3H)-dione, similar to unsubstituted 2-thiobarbituric acid, readily react with haloacetic acids and their

Full text of DOI:10.1023/B:RUGC.0000025180.58032.54

Russian Journal of General Chemistry, Vol. 74, No. 1, 2004, pp. 128 133. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 1, 2004,
pp. 139 145.
Original Russian Text Copyright
2004 by Fedorova, Meshcheryakov, Ganina, Moskvin, Ivin.
Azoles and Azines: CXIX.1 Alkylation
of 5,5 -(4-Nitrobenzylidene)bis(2-thiobarbituric) Acid
and 5-(4-Nitrophenyl)-2,8-dithioxo-5,7,8,9-tetrahydro-
2H-pyrano[2,3-d:6,5-d ]dipyrimidine-4,6(1H,3H)-dione
with Haloacetic Acids and Their Esters
E. V. Fedorova, M. P. Meshcheryakov, M. B. Ganina, A. V. Moskvin, and B. A. Ivin
St. Petersburg State Academy of Pharmaceutical Chemistry, St. Petersburg, Russia
Received February 13, 2003
Abstract 5,5 -(4-Nitrobenzylidene)bis(2-thiobarbituric) acid and 5-(4-nitrophenyl)-2,8-dithioxo-5,7,8,9-
tetrahydro-2H-pyrano[2,3-d:6,5-d ]dipyrimidine-4,6(1H,3H)-dione, similar to unsubstituted 2-thiobarbituric
acid, readily react with haloacetic acids and their esters to form regioselectively the S-alkylation products.
The alternative routes fo 5,5 -(4-nitrobenzylidene)bis[(4-hydroxy-6-oxo-1,6-dihydropyrimidine-5,2-diyl)-
sulfanyl]diacetic acids, based on condensation of 4,6-dihydroxypyrimidin-2-ylthioacetic acid with carbonyl
compounds followed by cyclodehydration to [(5-(4-nitrophenyl)-4,6-dioxo-3,5,6,7-tetrahydro-4H-pyrano[2,3-
d:6,5-d ]dipyrimidine-2,8-diyl)di(sulfanyl)]diacetic acid derivatives, are less efficient. Alkylation of 2-thio-
barbituric acid with ethyl bromoacetate in ethanol in the presence of alkali yields 5-(2-oxo-2,5-dihydro-1,3-
thiazol-4-yl)-2-thiobarbituric acid.
The derivatives of 5,5 -arylmethylenebis(polyhy-
droxypyrimidines) and 5H-pyrano[2,3-d:6,5-d ]dipyri-
midines prepared by us previously [2, 3] exhibit pro-
nounced antimicrobial, antiviral, antichlamydial, and
some other kinds of biological activity. However,
their essential drawback is low solubility in water and
in majority of organic solvents. One of the ways to
enhance the solubility is introduction of hydrophilic
(e.g., carboxymethyl) groups. Therefore, the goal of
this work was to develop procedures for preparing 5H-
pyrano[2,3-d:6,5-d ]dipyrimidine and 5,5 -arylmethyl-
enebis(polyhydroxypyrimidine) derivatives alkylated
with haloacetic acids and their esters, and to study the
structures and properties of these compounds.
with iodoacetic acid under the conditions when acid I
exists as a monoanion. To do this, we mixed aqueous
solutions of monosodium salt of acid I and sodium
monoiodoacetate (molar ratio 1 : 1, Scheme 1). Acid
IIa was isolated in 92% yield. The reaction of 2-thio-
barbituric acid I with ethyl bromoacetate was per-
formed in an aqueous-alcoholic (1 : 1 by volume) so-
lution of alkali at the reactant molar ratio of 1 : 1 : 1.
This method appeared to be very convenient from the
viewpoint of isolation of the forming ethyl ester IIb,
since under these conditions all the components of the
reaction mixture occur in solution, except the final
product precipitating in the course of the reaction.
Yield of chromatographically pure ester IIb 85%.
Ethyl
(4,6-dihydroxypyrimidin-2-yl)sulfanylacetate
Alkylation of barbituric acids and their derivatives
was studied very extensively [4 7]. In particular,
preparation of (4,5-dihydroxypyrimidin-2-ylsulfanyl)-
acetic acid IIa and its ethyl ester IIb by alkylation of
sodium 2-thiobarbiturate with monochloroacetic acid
and ethyl bromoacetate was reported [6, 7]. It is
known [8] that the 2-thiobarbiturate monoanion is
alkylated selectively at the S atom, which is due to
high polarizability of this reaction center. Therefore,
we performed alkylation of 2-thiobarbituric acid I
IIb is identical to the product obtained by esterifica-
tion of IIa (yield 78%).
We obtained an unexpected result that alkylation
of I with ethyl bromoacetate in ethanol in the presence
of alkali gives 5-(2-oxo-2,5-dihydro-1,3-thiazol-4-yl)-
2-thiobarbituric acid VII (Scheme 2) in 10 15% yield.
The mass spectrum of this compound contains a mo-
lecular peak with m/z 243 and fragmentation peaks
[M
HSCNN
HSCNN]+, [M
HSCNN
CHO]+, [M
H2NCOS]+, [M
HSCNN
CHO
H2CO]+, [M HSCNN CHO H2CO C CH]+,
For communication CXVIII, see [1].
and [M HSCNN CHO CHCOS]+. The H NMR
1
1
1070-3632/04/7401-0128 2004 MAIK Nauka/Interperiodica

AZOLES AND AZINES: CXIX.
129
Scheme 1.
O
O
N
HlgCH2CO2R
HN
HN
RO2CCH2S
O
OH
S
N
H
I
IIa, IIb
4-O2NC6H4CHO
4-O2NC6H4CHO
C6H4NO2-4
O
C6H4NO2-4
O
O
HN
N
O
NH
HlgCH2CO2R
NH
HN
OH HO
N
H
SCH2COR
RO2CCH2S
S
OH HO
III
S
N
H
N
H
H
IVa, IVb
(CF3CO)2O
(CF3CO)2O
C6H4NO2-4
O
C6H4NO2-4
O
O
O
HlgCH2CO2R
NH
HN
NH
HN
N
H
N
H
SCH2COR
RO2CCH2S
S
S
N
H
N
H
O
O
V
VIa, VIb
R = H (a), Et (b); Hlg = Cl, Br, I.
Scheme 2.
OH
N
OH
O
, H+
OH
N
HS
OH
N
C CH2
S
BrCH2COOEt
HBr
N
I
IIb
EtOH
OH
HS
OH
VIII
O
H2N
CH2
NH
C
S
N
OH
O
OH
H2O, H+
H+
S
C
N
N
NH4
OH
HS
N
OH
IX
HS
N
VII
spectrum of VII in DMSO-d6 contains low-field sig-
nals of labile protons of the NH and OH groups [
12.38 (2H), 12.08 ppm (1H)] and a singlet of the
methylene group [ 3.95 ppm (2H)], whereas the C5H
signals at 3.5 or 6 8 ppm typical of the tricarbonyl or
monoenol form of 2-thiobarbituric acid are absent.
The 13C NMR spectrum of VII in DMSO-d6 contains
seven carbon signals assignable to the C=N, C=O, and
CH2 groups of the thiazoline ring ( 177, 175.9, and
C
32.8 ppm, respectively) and to C2=S, C4=O, C6=O
groups and C5 atom (
174.2, 161.4, 161.6, and
C
93.8 ppm, respectively) of the pyrimidine ring. Com-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 1 2004

130
FEDOROVA et al.
1
Table 1. IR, UV, and H and 13C NMR spectra of (4,6-dihydroxypyrimidin-2-ylsulfanyl)acetic, 5,5 -(4-nitrobenzylidene)-
bis[(4-hydroxy-6-oxo-1,6-dihydropyrimidine-5,2-diyl)sulfanyl]diacetic, and [(5-(4-nitrophenyl)-4,6-dioxo-3,5,6,7-tetra-
hydro-4H-pyrano[2,3-d:6,5-d ]dipyrimidine-2,8-diyl)di(sulfanyl)]diacetic acids, their ethyl esters, and 5-(2-oxo-2,5-di-
hydro-1,3-thiazol-4-yl)-2-thiobarbituric acid (II VII)a
UV spectrum,
Comp.
no.
13C NMR spectrum,
, ppm
1
IR spectrum, , cm
max, nm 1H NMR spectrum, , ppm
(log )
IIa
465, 545, 600, 620, 680, 840, 855, 198 (4.27), 3.94 s (2H, SCH2), 5.19 s 32.16 (CH2S), 85.52 (C5),
900, 920, 930, 995, 1160, 1205, 268 (3.89) (1H, C5), 12.14 br.s (3H, 162.69 (C2), 167.42 (C4,6),
1235, 1285, 1305, 1345, 1375, 1470,
1550, 1620, 1670, 1735, 2325,
2530, 2665, 2730, 3290
NH, OH)
169.50 (COO)
IIb
480, 540, 590, 675, 870, 905, 930, 202 (4.22), 1.18 t (3H, CH3), 4.00 s (2H, 13.89 (CH3), 31.95 (CH2S),
990, 1010, 1025, 1150, 1165, 1210, 274 (3.89) SCH2), 4.08 d (2H, OCH2), 61.04 (CH2O), 85.51 (C5),
1240, 1290, 1300, 1350, 1370,
1400, 1560, 1630, 1670, 1730,
2340, 2520, 2670, 2735, 2970, 3295
5.21 s (1H, C5), 12.18 br.s 162.50 (C2), 167.50 (C4,6),
(2H, NH, OH) 168.27 (COO)
IVa 450, 500, 520, 545, 580, 605, 615, 196 (4.58), 3.99 s (4H, SCH2), 6.05 s 32.16 (SCH2), 32.63 (C ),
660, 680, 700, 735, 785, 800, 840, 288 (4.41) (1H, C H), 7.25 d (2H, HAr), 98.77 (C5), 123.19 (C3,5
860, 885, 980, 1020, 1065, 1115,
1165, 1190, 1270, 1310, 1360, 1380,
1470, 1520, 1565, 1655, 1730, 2290,
2520, 2720
8.10
d
(2H,
H
arom.), arom.), 127.77 (C2,6 arom.),
12.55 br.s (6H, NH, OH) 145.54 (C4 arom.), 149.16
(C1 arom.), 159.02 (C2),
166.20 (C4,6), 169.30 (COO)
IVb 490, 515, 540, 580, 615, 685, 755, 206 (4.42), 1.20 t (6H, CH3), 4.03 s (4H, 13.92 (CH3), 32.00 (SCH2),
770, 790, 810, 870, 950, 960, 1050, 272 (3.98) SCH2), 4.11 d (4H, OCH2), 34.85 (C ), 61.08 (CH2O),
1080, 1150, 1205, 1225, 1250, 1260,
1300, 1540, 1550, 1610, 1620, 1640,
1740, 2740, 3290
6.08 s (1H, C H), 7.25 d 102.75 (C5), 125.60 (C3,5
(2H, H arom.), 8.05 d (2H, arom.), 127.60 (C2,6 arom.),
H arom.), 12.50 br.s (4H, 145.05 (C4 arom.), 152.85
NH, OH)
(C1 arom.), 159.00 (C2),
167.05 (C4,6), 168.25 (COO)
VIa 490, 500, 550, 585, 620, 660, 760, 284 (4.58) 3.95 s (4H, SCH2), 4.85 s 32.25 (SCH2), 35.65 (C5),
790, 830, 935, 1030, 1090, 1130,
1150, 1180, 1210, 1250, 1280, 1310,
1350, 1510, 1600, 1660, 1760, 3140,
3250, 3420
1H, C5H), 7.50 d (2H, H 103.45 (C4a,5a), 125.40 (C3,5
arom.), 8.20 d (2H, H arom.), arom.), 127.15 (C2,6 arom.),
9.00 br.s (4H, NH, OH) 145.65 (C4 arom.), 152.60
(C1 arom.), 158.40 (C2,8),
166.20, 167.55 (C4,6,9a,10a)
169.20 (COO)
,
VIa 490, 500, 550, 585, 620, 660, 760, 202 (4.26), 1.16 t (6H, CH3), 4.00 s (4H, 13.88 (CH3), 31.92 (SCH2),
790, 830, 935, 1030, 1090, 1130, 268 (3.84) SCH2), 4.09 d (4H, OCH2), 34.78 (C5), 61.05 (CH2O),
1150, 1180, 1210, 1250, 1280, 1310,
1350, 1510, 1600, 1660, 1760, 3140,
3250, 3420
4.65 s (1H, C5H), 7.52 d (2H, 103.10 (C4a,5a), 126.30 (C3,5
H arom.), 8.18 d (2H, H arom.), 128.05 (C2,6 arom.),
arom.),9.30 br.s (2H, NH, 144.95 (C4 arom.), 152.10
OH)
(C1 arom.), 158.68 (C2,8),
167.25, 168.45 (C4,6,9a,10a),
169.15 (COO)
VII 470, 540, 595, 630, 670, 840, 850, 270 (3.94) 3.96
s
(2H,
SCH2), 32.85 (CH2), 93.77 (C5),
905, 920, 930, 990, 1165, 1205, 1230,
1280, 1300, 1340, 1380, 1465, 1550,
1615, 1665, 1730, 2320, 2530, 2660,
2730, 3295
12.25 br.s (4H, NH, OH) 161.42 (C6), 161.56 (C4),
174.20 (C2), 175.86 (C=O),
176.99 (C=N)
a 1
13
H and C NMR spestra of solutions in DMSO-d . IR spectra of mulls in mineral oil. UV spectra of aqueous or alcoholic solutions.
6
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 1 2004

AZOLES AND AZINES: CXIX.
Table 2. Yields, melting points, TLC retention factors, and elemental analyses of II VII
Found, %
131
Calculated
H
Comp.
no.
Yield,a Decomposition
point,
Rfb
Formula
%
C
C
H
N
C
N
IIa
IIb
92
181
0.22
0.83
35.45 3.15
41.56 4.47
13.69
11.99
12.92
11.73
13.33
12.02
13.72
C6C6N2O4S
35.64
41.74
42.46
46.54
43.93
48.00
35.64
2.97
4.35
2.79
3.88
2.50
3.65
2.97
13.86
12.17
13.04
11.80
13.49
12.17
13.86
85 (78)
87 (35)
81 (67)
86 (64)
84 (72)
5 (12)
188
201
305
192
212
230
C8C10N2O4S
C19C15N5O10S2
C23C23N5O10S2
C19C13N5O9S2
C23C21N5O9S2
C6C6N2O4S
IVa
IVb
VIa
VIb
VII
0.63c 42.27 2.95
0.72c 46.37 4.03
0.25
0.76
0.58
43.78 2.69
47.87 3.81
35.47 3.17
a
b
Yields of compounds prepared by procedures a and b (in parentheses).
9 : 1.5 : 0.5, unless otherwise indicated.
TLC: eluent ethyl acetate methanol acetic acid,
c
Eluent methanol acetic acid, 10 : 1.
pound VII may be formed by Scheme 2 involving
acylation of the C5 atom of I with the initially formed
ester IIb, yielding 5-[(4,6-dihydroxypyrimidin-2-ylsul-
fanyl)acetyl]-2-thiobarbituric acid VIII. The pyrimi-
dine ring in the acyl substituent of VIII is cleaved
with the hydrogen bromide released in alkylation,
transforming into isothiourea IX, which subsequently
recyclizes to the final product VII.
acetic anhydride yields, respectively, acid VIa or
ester VIb (yield 60 65%).
The purity of the products was checked by TLC;
the composition was determined by elemental anal-
1
ysis, and the structure, by H and 13C NMR, UV, and
IR spectroscopy (Tables 1, 2).
Compounds IIa and IIb are colorless. The other
compounds are cream-colored (IVa, IVb), yellowish
(VIa, VIb), or yellow (III, V). These are powdered
substances decomposing without melting on heating
to 180 230 C. Compounds IIa, IVa, and VIa are
poorly soluble in cold water and alcohol. Compounds
III and V are insoluble in water and poorly soluble in
DMSO. Ethyl esters IIb, IVb, and VIb are readily sol-
uble in DMSO and hot ethanol but insoluble in water.
5,5 -(4-Nitrobenzylidene)bis(2-thiobarbituric) acid
III and 5-(4-nitrophenyl)-2,8-dithioxo-5,7,8,9-tetrahy-
dro-2H-pyrano[2,3-d:6,5-d ]dipyrimidine-4,6(1H,3H)-
dione V were alkylated similarly to I. Aqueous solu-
tions of disodium salts of III and V were mixed with
an aqueous solution of sodium monoiodoacetate
(molar ratio 1 : 2). Apparently, in this case the reac-
tion regioselectivity is also high, as confirmed by the
purity and high yield ( 90%) of acids IVa and VIa
(Scheme 1). It was shown previously [9] that 5,5 -(4-
nitrobenzylidene)bis(2-thiobarbituric) acid III is hy-
drolyzed in a strongly alkaline solution to give 2-thio-
barbituric acid and the aldehyde as final products.
Since alkylation of acid III in alkaline solution is not
accompanied by its decomposition, the alkylation rate,
apparently, considerably exceeds the hydrolysis rate.
Ethyl esters IVb and VIb were prepared by esterifica-
tion of acids IVa and VIa.
The most characteristic signal in the 1H NMR
spectra of IIa and IIb in DMSO-d6 is the C5H signal.
Its presence proves the S-alkylation and not C5-alky-
lation. The signal is shifted downfield relative to the
similar signal in the spectrum of I and is observed
at 4.9 5.2 ppm. Furthermore, the spectra of IIa and
IIb, in contrast to that of I, contain a somewhat broad-
ened singlet at about 3.9 4.0 ppm corresponding to
methylene protons of the carboxymethyl fragment. In
the spectra of III, IVa, IVb, V, VIa, and VIb, the
characteristic signal is the methine proton singlet. In
the spectrum of III it is observed at about 6.1 ppm,
and in the spectrum of V it is shifted upfield to
4.8 ppm, which allows easy identification of bispyri-
midines III and pyranodipyrimidines V. In contrast to
the spectra of III and V, the spectra of their alkylation
products IV and VI contain somewhat broadened sin-
glets at 3.9 4.0 ppm, corresponding to the methylene
protons of the carboxymethyl fragment. The proton
signals of the other groups in the pyrimidine ring do
not noticeably change the position and shape upon
Acids IVa and VIa and their esters IVb and VIb
can be prepared not only by alkylation of III and V,
but also by condensation of acid IIa or its ester IIb
with 4-nitrobenzaldehyde followed by heterocycliza-
tion of bispyrimidines IVa and IVb.
In contrast to other 2-substituted 4,6-dihydroxy-
pyrimidines [10], compounds IIa and IIb enter into
the condensation very difficultly, transforming into
IVa and IVb only in 35 40 h, with the yield as low
as 35%. Heterocyclization of IVa or IVb in trifluoro-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 1 2004

132
FEDOROVA et al.
condensation, cyclization, and alkylation. The spectra
also contain broadened signals of NH and OH protons
(9.0 12.6 ppm) and signals of the aromatic ring pro-
tons (7.2 8.2 ppm). The spectra of esters IIb, IVb,
and VIb contain, in addition, the characteristic signals
of ethyl protons [1.2 (CH3) and 4.1 ppm (OCH2)].
cells at a layer thickness of 1 cm. The product purity
and reaction progress were monitored by TLC on
Silufol UV-254 plates, with UV detection or devel-
opment with iodine vapor. The melting or decomposi-
tion points were determined by the capillary method
without correction. Standard procedures were used for
dyring the solvents and purifying the products.
The 13C NMR spectra contain signals from sp3-
hybridized carbon atoms of the CH3, C , CH2S, and
CH2O groups (13.9, 31.9 32.2, 61.0 61.1 ppm),
from sp2-hybridized carbon atoms of the pyrimidine
ring: C5, C2, and C4, 6 (85.5 103.4, 158.0 162.7,
161.2 167.2 ppm, respectively), and from the carbo-
nyl carbon atom at 168.2 169.3 ppm.
5,5 -(4-Nitrobenzylidene)bis(2-thiobarbituric) acid
III and 5-(4-nitrophenyl)-2,8-dithioxo-5,7,8,9-tetrahy-
dro-2H-pyrano[2,3-d:6,5-d ]dipyrimidine-4,6(1H,3H)-
dione V were prepared according to [10].
(4,6-Dihydroxypyrimidin-2-ylsulfanyl)acetic
acid IIa. Sodium hydroxide (0.024 mol) and 2-thio-
barbituric acid I (0.024 mol) were dissolved in 100 ml
of water (pH of solution 8 9), and a solution of
0.024 mol of monoiodoacetic acid and 0.024 mol of
alkali in 100 ml of water (pH of solution 11 12) was
added dropwise. The mixture was stirred for 2 h at
50 C. In the process, the solution pH decreased to
5 6. After cooling, the mixture was acidified with
10% HCl to pH 1 2. The resulting colorless precipi-
tate was filtered off, washed with cold water, and
dried.
The UV spectra of aqueous-alcoholic solutions of
the compounds under consideration contain strong
bands assignable to
* transitions in the -elec-
tron systems of aromatic and pyrimidine fragments,
with two maxima in the ranges 196 206 and 268
288 nm. There are no significant differences between
the spectra of noncyclized (III, IV) and cyclized (V,
VI) compounds.
The IR spectra of II VI (mulls in mineral oil) also
confirm their structure. The most characteristic are the
stretching vibration bands of O H and N H groups
Ethyl (4,6-dihydroxypyrimidin-2-ylsulfanyl)-
acetate IIb. a. Hot water in amount ( 20 ml) required
to obtain a homogeneous solution (pH 10) was added
to a refluxing suspension of 0.035 mol of 2-thiobarbi-
turic acid I and 0.035 mol of NaOH in 35 mol of eth-
anol. After cooling to 50 C, a solution of 0.035 mol
of ethyl bromoacetate in 15 ml of alcohol was added.
The mixture was stirred for 2 h at 45 50 C. After
cooling to 20 25 C, colorless crystals of ethyl ester
IIb were obtained. The precipitate was filtered off,
washed with cold water, and dried.
1
(3050 3150 cm ) and a strong vibration band of the
1
C=O group (1720 1730 cm ).
Thus, from the viewpoint of the yield and purity
of the final products, synthesis of 5,5 -(4-nitrobenzyl-
idene)bis[(4-hydroxy-6-oxo-1,6-dihydropyrimidine-
5,2-diyl)sulfanyl]diacetic acid IVa and its ester IVb
by alkylkation of 5,5 -(4-nitrobenzylidene)bis(2-thio-
barbituric) acid III with iodoacetic acid or ethyl bro-
moacetate is preferable over condensation of (4,6-di-
hydroxypyrimidin-2-ylsulfanyl)acetic acid with 4-ni-
trobenzaldehyde. For the synthesis of [(5-(4-nitro-
phenyl)-4,6-dioxo-3,5,6,7-tetrahydro-4H-pyrano[2,3-
d:6,5-d ]dipyrimidine-2,8-diyl)di(sulfanyl)]diacetic
acid (VIa) derivatives from 5,5 -(4-nitrobenzylidene)-
bis(2-thiobarbituric) acid III, the sequence of the al-
kylation and cyclization steps is not essential from
the viewpoint of the product yield and reaction time.
b. A mixture of 0.005 mol of acid IIa, 30 ml of
ethanol, and two or three drops of H3PO4 was re-
fluxed for 2 h. The solvent was distilled off, and the
residue was crystallized from water.
5,5 -(4-Nitrobenzylidene)bis[(4-hydroxy-6-oxo-
1,6-dihydropyrimidine-5,2-diyl)sulfanyl]diacetic
acid IVa. a. A solution of 0.048 mol of monoiodo-
acetic acid and 0.048 mol of NaOH in 100 ml of water
(pH 11 12) was added dropwise to an aqueous solu-
tion of 0.048 mol of NaOH and 0.024 mol of acid III
(pH 8 9). The mixture was stirred for 2 h at 50 C
(pH decreased to 5 6), cooled, and acidified with
10% HCl to pH 1 2. The precipitate (colorless flakes)
was filtered off, washed with cold water, and dried.
EXPERIMENTAL
1
The H and 13C NMR spectra (solutions in DMSO-
d6) were recorded on Bruker AM-200 (200 and
50 MHz, respectively) and Bruker AM-500 (500 and
125 MHz, respectively) spectrometers, internal refer-
ence DMSO. The IR spectra (mulls in mineral oil)
were recorded on a Specord IR-75 spectrophotometer.
The electronic absorption spectra (aqueous solutions)
were taken on an SF-56 spectrophotometer in quartz
b. A solution of 0.00275 mol of 4-nitrobenzalde-
hyde in 10 ml of ethanol was added dropwise to a
solution of 0.005 mol of acid IIa in 30 ml of ethanol.
The mixture was stirred for 35 h at 55 60 C. The
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 1 2004

AZOLES AND AZINES: CXIX.
133
solvent was distilled off, and the residue was crystal-
lized from water.
20 ml of ethanol. The precipitate that formed within
30 min was filtered off, washed with alcohol, and
dried.
Diethyl 5,5 -(4-nitrobenzylidene)bis[(4-hydroxy-
6-oxo-1,6-dihydropyrimidine-5,2-diyl)sulfanyl]di-
acetate IVb. a. Hot water in an amount ( 30 ml)
required to dissolve acid III (pH 10) was added to a
solution of 0.035 mol of acid III in 50 ml of hot
alcoholic NaOH (0.07 mol). The solution was cooled
to 50 C, and a solution of 0.07 mol of ethyl bromo-
acetate in 15 ml of alcohol was added. The mixture
was stirred at 45 50 C for 2 h. After cooling, the
precipitate of IVb was filtered off, washed with cold
water, and dried.
ACKNOWLEDGMENTS
The study was financially supported by the Minis-
try of Education of the Russian Federation, project
no. 168 for the years 2001 2002 in the field of natural
sciences.
REFERENCES
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 1 2004